Novel Ambulatory and Cognitive Biomarkers in Relapsing-Remitting MS

Investigators examined the relationships between morphological and diffusional properties in cerebral gray matter and physical and cognitive performance in patients with relapsing-remitting MS.

Cortical diffusion and thalamic volume may serve as predictive biomarkers for walking and cognitive impairments in patients with relapsing-remitting multiple sclerosis (RRMS), according to study findings published in the Journal of Neurology.

The study included 67 patients with RRMS from a randomized trial that investigated the effects of long-term exercise on brain atrophy in patients with multiple sclerosis. Patients underwent the brief repeatable battery of neuropsychological tests (BRB-N), the 6 minute walk test (6MWT), and the 6-spot step test (SSST).

Study participants also underwent magnetic resonance imaging scans using structural and diffusion kurtosis imaging (DKI) protocols. The study investigators analyzed gray matter (GM) volume metrics and DKI measurements in the cortex as well as deep GM structures.

Higher cortical mean diffusivity (MD) was associated with poor performance on the SSST. The significant positive association between cortical MD and SSST was observed unilaterally in the occipital gyrus as well as bilaterally in the parietal lobe, precuneus, cingulate gyrus, cuneus, superior, and middle frontal gyrus.

The study investigators also found a negative correlation between MD and the 6MWT unilaterally in the inferior parietal lobule, postcentral gyrus, and inferior frontal sulcus, as well as bilaterally in the superior and middle frontal gyrus. Decreased thalamic volume correlated with a longer time to complete the SSST.

Overall, thalamic volume correlated with the SSST (r2=0.21), 6MWT (r2=0.18), information processing (r2=0.21), and white matter lesion volume (r2=0.60).

Limitations of the study included its small sample size and lack of a matched healthy control group.

The study investigators concluded that their findings “indicate that cortical DKI and thalamic volume could serve as a biomarker of walking and cognitive impairments in” patients with RRMS.

Disclosure: One study author declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Nygaard MKE, Langeskov-Christensen M, Dalgas U, Eskildsen SF. Cortical diffusion kurtosis imaging and thalamic volume are associated with cognitive and walking performance in relapsing-remitting multiple sclerosis. J Neurol. Published online April 7, 2021. doi:10.1007/s00415-021-10543-4